journal article·2024-08Open access

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2‐VSIR Axis in Glycogen Storage Disease

Jiaoli Lan, Yuxin Zhang, Cuiyuan Jin, Huan Chen, Zexiong Su, Jiaxing Wu, Ni Ma, Xiaoyan Zhang, Yiyun Lu, Yongxin Chen, Xiaolu Zeng, Huiqiong Zhang, Guilang Zheng, Yueyu Sun, Chun Wang, Yan Hu, Yifei Wang, Yumei Liu, Zhaoyang Zeng, Liyun Shi, Jun He, Aihua Cao, Yichao Wang, Xu Pan, Gulei Jin, Ying Wang, Xun Jiang, Huiqing Shen, Qing Tang, Xiaoli Xie, Yuan Xiao, Xuemei Zhong, Xuchao Zhang, Liang Zeng, Liping Ye, Jing Xie, Lanlan Geng, Zhiling Li, Xiaohui Wu, Ying Wang, Ren Mao, Shaojun Zhang, Siyuan Huang, Suling Liu, Hanshi Zeng, Wanfu Xu, Sitang Gong, Yuxiong Guo, Min Yang

Advanced Science· Volume 11· Issue 30

Abstract

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Immunodeficiency and Autoimmune Disorders · Cystic Fibrosis Research Advances · Dysphagia Assessment and Management

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pediatrics Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Southern Medical University Guangzhou 510080 China

Research Center of Medical Sciences Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou 510080 China

Nanfang Hospital Southern Medical University Guangzhou 510515 China

Institute of Translational Medicine Zhejiang Shuren University Hangzhou 310015 China

Department of Gastroenterology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China

Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University Changsha 410007 China

Department of Pediatrics Shandong University Qilu Hospital Jinan Shandong 250063 China

National Health Commission (NHC) Key Laboratory of Birth Defect for Research and Prevention Hunan Provincial Maternal and Child Health Care Hospital Changsha Hunan 410008 China

Department of Basic Medical Sciences School of Medicine Tsinghua University Beijing 100084 China

Institute of Bioinformatics College of Agronomy and Biotechnology Zhejiang University Hangzhou Zhejiang 277599 China

Division of Pediatric Gastroenterology and Nutrition Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200092 China

Department of Pediatrics The Second Affiliated Hospital Air Force Military Medical University Xi'an 710032 China

Department of gastroenterology Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing 100045 China

Department of Pediatrics The First Affiliated hospital of Guangxi Medical University Nanning 530021 China

Chengdu Women's and Children's Central Hospital School of Medicine University of Electronic Science and Technology of China Chengdu 610073 China

Department of Pediatrics Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

Department of gastroenterology Capital Institute of Pediatrics No. 2 Yabao Road Beijing 100020 China

Guangdong Lung Cancer Institute Medical Research Center Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou 510080 China

Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou 510080 China

Department of pathology Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China

Department of Gastroenterology The First Affiliated Hospital Sun Yat‐Sen University Guangzhou 510062 China

Academy for Advanced Interdisciplinary Studies Peking University Beijing 100091 China

Clinical Laboratory Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou 510080 China

Funding

National Natural Science Foundation of China

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